1. Field of the Invention
A low cost tabletop x-ray bone densitometer capable of measuring bone density in the human body.
2. Description of the Prior Art
Bone density has been directly associated with bone strength and the risk for non-traumatic fractures. Early detection of low bone mass and the application of appropriate therapies is of significant medical value. The ability to monitor therapy effectiveness by detection of small changes in bone density is also of value. Because of the vast need for diagnosis and the high cost of existing devices, there is an unmet need for a low cost bone densitometer with adequate sensitivity for widespread screening of patients at risk for osteoporosis. The immediate readout, low cost, ease of use, and method of calibration provide important advances to the prior art. This invention has the potential to readily provide bone densitometry tests to millions of patients who currently do not, or can not, afford the more involved and costly exams.
Various non-invasive methods for bone density measurements have been developed. These include Quantitative Computed Tomography (QCT), Single Photon and Dual Photon Absorptiometry (SPA and DPA), Dual Energy X-ray Absorptiometry (DXA), peripheral dual energy x-ray absorptiometry (pDXA) and Radiographic Absorptiometry or Micro-densitometry (RA). All of these techniques utilize the difference in x-ray or gamma ray attenuation of bone and soft tissue components. Use of dual energy methods improves on the ability to separate overlying soft tissues from bone in the measurement. The different techniques are largely separated based on the particular bone to be measured and the quantity of surrounding soft tissue. For example, QCT measures the central bone of the spine, which is surrounded by much tissue, while pDXA typically measures the radius, which has little overlying tissue. Osteoporosis is believed to be a systemic disease process, but it is well known that different regions of the skeleton lose bone at different rates.
The QCT method uses a x-ray CT Scanner to generate a cross sectional slice through three to four lumbar vertebra. Typically a bone and tissue equivalent phantom is scanned simultaneously with the patient to provide calibration.
With the SPA and DPA methods, x-rays from a radioactive source such as Gd153 are employed as the source. These methods allow measurements at both the extremities and central skeleton sites and, in the case of DPA, uses dual energy techniques. These techniques have largely been replaced with the newer DXA devices due to the long exam times and need to periodically replace the isotope source.
DXA and pDXA have become widely used in clinical practice. The use of filtered x-ray sources, in place of radioactive isotopes, has improved precision, exam speed and long term reliability. DXA techniques use a scanning x-ray source in a rectilinear fashion to cover the target body part. An image of the body is created showing regions of bone and soft tissue and requires software to find the bone images and edges of bone for measurement. In the DXA approach, the x-ray tube and a point imaging detector are scanned over the target region in a roster fashion resulting in the point-by-point transmission of the beam through the bone and surrounding soft tissue. Point source or more recently fan beam geometries and line detector arrays are used requiring some significant time to complete the mechanical scan. In addition, a mechanical structure is required to reproducibility move the x-ray source and x-ray detectors over the body. The measurement Region of Interest (ROI) is determined in software by finding bone regions. The x-ray source output must be maintained within close limits during the scan, placing stringent electrical stability requirements on both the high voltage power supply and the x-ray tube current throughout the scan. In addition, electrical analysis of pulse height and energy separation is required in the x-ray pulses used to create the images. DXA nevertheless provides bone mineral density, ("BMD"), measurements throughout the skeleton system with low radiation dose and good precision. Whole body DXA devices are expensive and generally require a room size facility for their operation. In response to these limitations, pDXA (peripheral DXA) devices have been developed more recently which are smaller and less expensive. The measurement target is usually the distal radius, although the calcaneous is also measured. One challenge of pDXA devices is the need to reproduce the measured region of interest (ROI) precisely, to maintain high precision in follow up clinical studies. Although of smaller size and lower cost, pDXA devices also use rectilinear scanning techniques as in whole body DXA devices, thus requiring a more complex mechanical design and associated expense. PDXA devices also create an image of the target bone requiring software to define the measurement ROI. PDXA devices require similar controls as the larger DXA machines, on the power supply and detector response over the entire scan time. Scanning pDXA devices remain relatively expensive for widespread clinical use in primary care physician offices.
In recent years, the older technique of microdensitometry has been revived as radiographic absorptiometry (RA). A representative system is marketed by COMPUMED, which provides a mail order service to analyze the x-ray films and provide clinical reports. With RA, a finger bone is exposed simultaneously with a reference aluminum step wedge to x-rays. The image is recorded with direct exposure x-ray film and processed in a standard film processor. The developed films are then scanned with a photo densitometry to record the density patterns of both the target bone and the aluminum step wedge. The aluminum step wedge becomes the calibration phantom for reference to the bone absorption. Although the initial cost to use the service is low (cost of the aluminum step wedge and x-ray film), this approach has several major drawbacks. First, the user must have a complete x-ray system, x-ray generator and x-ray tube, available for use as well as a film processor. These are relatively expensive devices, and are not available in the vast majority of primary care physician offices. The scanning photo densitometer to read the films must have acceptable performance and reliability, thus adding additional costs. Film processors can vary in performance, sometimes producing streaks and artifacts, which need to be accounted for at the film scanning stage. The exposed and processed films must be mailed to a central processing facility, necessitating important delays in obtaining the final clinical results. The use of aluminum to calibrate for bone density is far from optimal. Although aluminum is close to bone in physical density, if differs in atomic composition, and is not an adequate reference for bone for highly consistent results. Human bone is composed largely of calcium hydroxyapatite in the presence of soft tissue components, blood and fat. The x-ray attenuations of these tissues are dependent on their physical density, their effective atomic numbers, and the energy of the x-ray beam. The x-ray beam spectrum produced by x-ray systems is dependent upon many variables, including the primary kilo voltage applied to the tube, its waveform, inherent and added filtration, x-ray tube target angle, x-ray tube aging and target changes with over exposures, and in some cases, the quality of the line voltage and its stability. In short, x-ray systems from different manufacturers, and in use at different clinics, produce different x-ray beam spectra. These differences in beam energy are important for highly precise quantitative measurements. We have shown with earlier measurements that aluminum may have limitations for accurate calibrations of bone across beam energy changes which may occur with different x-ray systems in use at various radiographic clinics.
The radiation beam in bone densitometers is typically collimated to the desired region of interest before reaching the patient, to reduce radiation dose and improve image quality. Different shaped beams have been used, including pencil beam, fan beam, and cone beam shapes. The beam and the opposing detector should have corresponding geometries. Pencil and fan beam geometry requires scanning, and is coupled to point or line detectors to create images of the bone. Area detectors, such as flat panel silicon arrays, or x-ray film, make it possible to obtain full field area simultaneous exposures of the total body part and calibration reference on a single exposure, and are used in RA techniques, for example, as well as the current invention with modifications.
U.S. Pat. No. 5,365,564, November 94, by Yashida, et al, teaches a method and apparatus for bone morphometry on extremities bones. This method uses x-ray film and illuminating light to obtain morphometric details on bone with semi automatic analysis. The system uses aluminum as the reference standard matter. The system does not propose to measure bone density, and has the undesirable features of using x-ray film and aluminum for reference. U.S. Pat. No. 4,721,112, January 1988, by Hirano, teaches a bone evaluation method that requires determining a bone pattern and calculating a bone index. The bone density distribution is classified by color, and an image is used to produce a bone pattern.
Methods and an apparatus for positioning and placement of measurement regions at a selected distance from a styloid bone tip are taught in U.S. Pat. No. 5,005,196, April 1991, and U.S. Pat. No. 5,138,553, August 1992, by Lanza, et al. The patents employ radiographic imaging devices and describe software methods to reproducibly position ROIs in the images of the radius and ulna. The apparatus employs limb positioning and instrument calibration methods, typically for the wrist, which uses a pair of side blocks and a clamping mechanism to immobilize the limb. The blocks are of different absorptive properties for calibrating the images.
U.S. Pat. No. 5,187,731, February 1993, by Shimura, hereby incorporated by reference, teaches a method for analysis of bone calcium using a plurality of recording media and different kinds of radiation, referenced by a bone calcium material and producing a plurality of radiation images. In one embodiment, a stimulable phosphor sheet is exposed to one exposure of energy A, and thereafter, sheet A is quickly removed from the position for x-ray exposure and stimulable phosphor sheet B is quickly set in place at the same position, for exposure to x-rays of energy B. At the same time, the tube voltage of the x-ray source is changed to produce x-rays of the different energy B. A bone reference material with a plurality of radiation absorption amounts is placed on each of the sheets. The stimulable phosphor sheets are later read out by scanning laser beam deflected by a scanning mirror. The emitted light from the sheet is recorded by a photo multiplier tube, to generate the final electronic image. In a second embodiment, stimulable phosphor sheets A and B are placed one upon the other, and a filter is inserted between the sheets. The filter produces a second, different energy spectrum at the second sheet following a single x-ray exposure. This method has the disadvantage of cost, significant time to change the detector sheets, causing patient motion, and the complex and expensive readout of stimulable phosphors.
Prior art scanning DXA systems, such as U.S. Pat. Nos. 5,040,199 and 4,811,373 to Stein, require multiple reference detectors with differing absorbers are used by the system to continuously correct for variations in voltage and current of the x-ray tube. Stein teaches to insert into and remove from the x-ray beam a piece of bone-like calibration material of predetermined constant thickness, such that the regions of the patient are exposed both to the x-ray beam and to the beam obstructed by said predetermined thickness of bone-like material.
Dissing's U.S. Pat. No. 3,944,830, March 1976, teaches the use of two different photon energies in a scanning apparatus for bone density measurements. Mackey's U.S. Pat. No. 4,852,137, July 1989, discloses an imaging apparatus using x-rays detected by a cooled charge couple device, (CCD), containing two dimensional imaging array of sensors containing numerous pixcels on the order of 250,000 sensor elements which are sensitive to light coupled by a lens to a phosphor, which emits visible light following the x-ray exposure and utilizes a shutter. Mouyen, in U.S. Pat. No. 4,593,400, discloses an x-ray apparatus for imaging which uses an x-ray system, a phosphor screen which converts x-rays to lights, a lens, shielding and collimation, recorded by a charge-coupled device (CCD).
Karallas, in U.S. Pat. No. 5,465,284, November 1995 and U.S. Pat. No. 5,150,394, September 1992, discusses a dual energy system for quantitative radiographic imaging. The system uses an area scanning technique to minimize scanning time. An x-ray source produces two different energy levels from two different exposures, the image is sensed by a scintillator to convert x-rays to light, a lens or fiber optic coupler, shielding, and collimation, recorded by a binnable charge-coupled device (CCD). Quantitative information regarding the object being imaged uses standard dual photon absorptiometry techniques. An internal instrument stability control system provides compensation for any instability in the x-ray tube potential and current. The tube output is monitored by a pair of x-ray sensors placed at a secondary beam port near the tube window.
Weil, in U.S. Pat. No. 5,712,892, January 1998, discloses an x-ray apparatus for measuring bone density of the extremities which uses a calibration wedge, an x-ray image converter, and a digital image processor. Images are produced in an area photodetector array to automatically measure bone density by undisclosed methods.
U.S. Pat. No. 5,852,647 by Schick discusses a method and apparatus for bone density measurements in the hand using hard tissue (aluminum) and soft tissue (epoxy) references. Dual energy exposures are recorded on the area radiation sensor to create high and low energy images. The sensor may be CMOS active pixel sensor arrays, or CCD area arrays, which are optically coupled to phosphorescent material by lens or optical fibers, as in Karellas and other, or are coupled directly on the face of the sensor. In all cases, an image is created which contains an area array of pixels. An iterative process is used to remove soft or hard tissue components to arrive at an aluminum equivalent density. The location of the bones within the image is determined by a thresholding procedure, and the measured region of interest includes any bone region which is positioned and imaged within the sensor's field of view.
All of the above discussed methods either using mechanical scanning or area imaging detectors containing many imaging elements, such as CCD cameras. They require the use of software techniques to detect bone edges from the two dimensional array of pixel elements and to define and locate the ROI of measurement. Measurements are made in bone regions outlined by pixels of varying signal levels defined by software techniques. These methods utilize either single or dual energy x-ray exposures which are calibrated by references placed at the x-ray source or alternatively use aluminum placed in the object plane.